Medicine dark side of the drug cancer therapy

Researchers dealt with the downsides of drug cancer treatment

More and more people are getting cancer. The serious illness is also combated in many cases with drugs. German researchers have now dealt with the dark side of the drug therapy of cancer.

Number of cancer cases almost doubled since 1970

According to the World Cancer Report of the International Agency for Research on Cancer (IARC), there could be 20 million cancer cases annually by 2025. In this country too, more and more people are affected. The number of new cases in Germany has almost doubled since 1970. Patients are often treated with medication. Scientists from the Charité - Universitätsmedizin Berlin and the Max Delbrück Center for Molecular Medicine (MDC) have dealt with the downsides of this therapy and have now published their findings in the journal "Nature".

More and more Germans are getting cancer. Researchers have now dealt with the dark side of the drug therapy of cancer. (Image: contrastwerkstatt / fotolia.com)

Prevent tumor cells from further growth

When malignant changes threaten the cells of our bodies, built-in self-protection programs intervene and so often prevent carcinogenesis.

Two of these tumor suppressor mechanisms are programmed cell death, called apoptosis, and the acute induction of a cell aging program called senescence. The mechanisms prevent cell division and tumor growth.

Even with chemotherapy, these programs are activated and mediate the anti-tumor effect.

The team around Prof. Dr. med. Clemens A. Schmitt, director of the Charité Center for Molecular Cancer Research and researchers at the MDC and the German Consortium for Translational Cancer Research (DKTK), have already shown several years ago that switching on cellular senescence is an important and desirable feature of the often apoptosis-defective tumor cells Therapy effect is to prevent the tumor cells from further growth.

Particularly threatening ability of tumor cells

In his new study, the research team observed that the growth-blocked tumor cells undergo massive epigenetic reprogramming as they enter the senescence state.

This involves re-encoding various cellular work programs, including turning on a stem cell program, also known as tumor stemness.

Tumor Stemness describes the particularly threatening ability of tumor cells to drive or even restart tumor growth, as is the case, for example, with the development of secondary tumors.

Since the stem cell function is necessarily coupled with cell division, the cancer researchers have investigated whether switching off individual genes absolutely necessary for the senescence preservation could make the newly acquired stem cell capacity of the formerly senescent cells functionally visible.

In fact, the previously senescent tumor cells behaved much more aggressively than the same tumor cells that never entered the senescence state.

Study results provide insight into the clever behavior of tumor cells

Investigations in in vivo tumor models confirmed the relevance of these cell culture findings.

Using a new single-cell tracking technique, the scientists were also able to show that senescent tumor cells rarely can spontaneously reenter the cell division cycle.

A comparison of tumor specimens in lymph node cancer before initiation of therapy and later in the relapse of the same patients suggested that just such senescent cells after chemotherapy contribute to the particularly aggressive tumor growth in treatment failure.

"These results are clinically very important because they give us insight into the clever behavior of the tumor cells to prevail against actually very effective cancer treatments," explains Prof. Schmitt.

"Fortunately, in this research, we also presented genetic and drug strategies that directly attack and neutralize the newly acquired tumor stemness of previously senescent tumor cells," he adds.

In follow-up experiments and a currently planned clinical study, the scientists led by Prof. Schmitt, who as a lymphoma specialist treated daily patients with lymphoma cancer in the Charité, the role of senescence-associated stem cell reprogramming in lymphoma patients to pursue a targeted therapeutic approach to come closer. (Ad)